Respiratory Viruses: Influenza & Measles – Structure, Pathogenesis, Immunity, and Control

Respiratory Viruses: Overview

Respiratory viruses are a major cause of morbidity and mortality worldwide, particularly in children. Acute respiratory infections account for approximately 1/5 of all childhood deaths. The most common viral agents include influenza viruses and measles virus, among others.

• Key Respiratory Viruses: Influenza, Measles, Rhinoviruses, Coronaviruses, Adenoviruses, Respiratory Syncytial Virus (RSV), Parainfluenza viruses, Human Metapneumovirus, Bocaviruses, Sarbecoviruses, and Merbecoviruses.

• Clinical Impact: Range from mild upper respiratory tract infections to severe pneumonia and systemic complications.

• Critical Care: Severe cases may require interventions such as Extracorporeal Membrane Oxygenation (ECMO).

Orthomyxoviridae: Influenza Viruses

History and Epidemiology

Influenza has affected humans for over 1500 years, with pandemics causing significant mortality. The 1918 Spanish flu pandemic killed an estimated 50–100 million people worldwide.

• Major Pandemics:

  • 1918 – Spanish flu (H1N1): 50–100 million deaths

  • 1957–58 – Asian flu (H2N2): 2 million deaths

  • 1968–69 – Hong Kong flu (H3N2): 1 million deaths

  • 1997 – Bird flu (H5N1): 352 deaths since first case

  • 2009 – Swine flu (H1N1): 18,000 deaths

• Annual Global Impact: >1 billion infections, 5 million severe cases, 250,000–600,000 deaths (WHO estimates).

• At-Risk Groups: Very young, elderly, and immunocompromised individuals.

Classification and Structure

• Family: Orthomyxoviridae

• Genera: Influenzavirus A, B, C, D

• Host Range: Humans, pigs, horses, birds, seals, whales, cattle, small ruminants

• Virion Structure: Enveloped, 80–120 nm diameter, 8 segments of negative-sense single-stranded RNA

Type	Host Species
Influenza A	Humans, horses, pigs, mink, seals, whales, fowl
Influenza B	Humans
Influenza C	Humans, pigs
Influenza D	Cattle, pigs, humans, small ruminants

Genome Organization

• 8 RNA segments (13.5 kb total)

• Encodes proteins such as polymerase subunits (PA, PB1, PB2), hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), matrix proteins (M1, M2), and non-structural proteins

Life Cycle

• Attachment via HA to sialic acid receptors

• Endocytosis and fusion with endosomal membrane

• Release of viral RNA into cytoplasm, transport to nucleus

• Transcription and replication of viral RNA

• Assembly and budding from host cell membrane

Pathogenesis and Disease

• Mild Disease: Fever, sore throat, cough, headache, muscle pain, fatigue

• Severe Disease: Pneumonia, secondary bacterial infections, acute respiratory distress syndrome (ARDS)

• Non-respiratory Complications: Cardiac, neurological, and other systemic effects

Immunity

Innate Immunity

• Recognition of viral RNA by pattern recognition receptors (PRRs) such as RIG-I

• Induction of type I and III interferons (IFNs), pro-inflammatory cytokines, and antiviral proteins (e.g., OAS1, Mx1, IFITM3)

• Neutrophil and macrophage responses limit viral replication but may contribute to lung damage if dysregulated

Adaptive Immunity

• T cell immunity: CD4+ T cells help B cell activation; CD8+ cytotoxic T cells clear infected cells

• B cell immunity: Production of neutralizing antibodies (IgG, IgA) against HA, NA, and NP

• HLA polymorphism: Influences susceptibility and immune response to different influenza strains

Factors Influencing Disease Severity

• Host factors: Age, genetic susceptibility, obesity, underlying conditions, sex hormones, microbiome, pre-existing immunity

• Viral factors: Strain virulence, viral load, immune evasion mechanisms

Control and Prevention

• Vaccines: Annual vaccines target prevalent strains; effectiveness varies

• Antivirals: Oseltamivir (Tamiflu), Zanamivir (Relenza)

• Surveillance: Critical for early detection and response to emerging pandemic strains

Paramyxoviridae: Measles Virus and Related Viruses

Characteristics

• Enveloped viruses, 150–300 nm diameter

• Single-stranded, negative-sense RNA genome (13–19 kb)

• Genome encodes up to 12 proteins

• Sensitive to heat, UV, detergents, and low pH

Family Tree and Phylogenetics

• Includes Parainfluenza virus, Mumps virus, Respiratory Syncytial Virus (RSV), and Morbillivirus (e.g., Measles virus)

• Morbillivirus genus includes animal pathogens (canine, phocine, rinderpest, etc.) and human measles virus

Measles Virus (MeV): Background and Epidemiology

• Highly infectious (R0 = 12–18)

• Pre-vaccine era: nearly universal childhood infection, ~2 million deaths/year

• Currently: >100,000 deaths/year globally, vaccine-preventable

Clinical Features and Complications

• Symptoms: Cough, coryza (runny nose), conjunctivitis, Koplik spots, maculopapular skin rash

• Complications: Otitis media, pneumonia, encephalitis, blindness (linked to vitamin A deficiency), death (1 in 5000 cases), long-term risk of subacute sclerosing panencephalitis (SSPE)

Measles Virus Structure and Genome

• Enveloped, 120–250 nm diameter

• Genome: 16 kb negative-sense ssRNA encoding N, P, M, F, H, L proteins

• P gene encodes immunomodulatory proteins (C and V) that suppress interferon responses

Protein	Function
Nucleocapsid (N)	Encapsidates viral RNA
Phosphoprotein (P)	Polymerase cofactor, immunomodulation
Matrix (M)	Virion assembly
Fusion (F)	Membrane fusion
Haemagglutinin (H)	Attachment to host cell
Large (L)	RNA-dependent RNA polymerase

Life Cycle of Measles Virus

• Attachment to host cell via SLAM (CD150) receptor

• Fusion and entry, release of viral RNA

• Transcription and translation of viral proteins

• Assembly and budding from host cell membrane

Pathogenesis and Immune Response

• Initial infection blunts innate immune response (suppression of type I IFN)

• Extensive viral replication and spread during a refractory period (10–14 days)

• Prodrome: fever, coryza, cough, conjunctivitis, followed by rash

• Rash phase: coincides with MeV-specific cytotoxic T cell response and viral clearance

• Unique feature: Immunological amnesia – depletion of pre-existing memory B cells, increasing susceptibility to other pathogens

Prevention and Vaccination

• Measles vaccine introduced in 1968; MMR (measles, mumps, rubella) vaccine introduced in 1996

• Vaccination dramatically reduced incidence and mortality

• Vaccine hesitancy (e.g., anti-vaccine misinformation) can lead to outbreaks

Summary Table: Influenza vs. Measles Virus

Feature	Influenza Virus	Measles Virus
Family	Orthomyxoviridae	Paramyxoviridae
Genome	8 segments, (-)ssRNA	Non-segmented, (-)ssRNA
Envelope	Yes	Yes
Major Antigens	HA, NA	H, F
Transmission	Respiratory droplets	Respiratory droplets
Vaccine	Annual, strain-specific	MMR (live attenuated)
Complications	Pneumonia, ARDS, secondary infections	Pneumonia, encephalitis, SSPE, immune amnesia

References and Further Reading

• Principles of Virology (Flint et al.)

• Medical Virology (Zuckerman et al.)

• Introduction to Modern Virology (Dimmock et al.)

Additional info: This guide expands on lecture slides by providing definitions, context, and comparative tables for exam preparation.